Structure-selected RBM immunogens prime polyclonal memory responses that neutralize SARS-CoV-2 variants of concern
Structure-selected RBM immunogens prime polyclonal memory responses that neutralize SARS-CoV-2 variants of concern
Abstract Successful control of the COVID-19 pandemic depends on vaccines that prevent transmission. The full-length Spike protein is highly immunogenic but the majority of antibodies do not target the virus: ACE2 interface. In an effort to concentrate the antibody response to the receptor-binding motif (RBM) we generated a series of conformationally-constrained immunogens by inserting solvent-exposed RBM amino acid residues into hypervariable loops of an immunoglobulin molecule. Priming C57BL/6 mice with plasmid (p)DNA encoding these constructs yielded a rapid memory response to booster immunization with recombinant Spike protein. Immune sera antibodies bound strongly to the purified receptor-binding domain (RBD) and Spike proteins. pDNA primed for a consistent response with antibodies efficient at neutralizing authentic WA1 virus and two variants of concern (VOC), B.1.351 and B.1.617.2. These findings demonstrate that immunogens built on structure selection can focus the response to conserved sites of vulnerability shared between wildtype virus and VOCs and induce neutralizing antibodies across variants.
Gao George F.、Carlin Aaron F.、Wu Yan、Kouznetsova Valentina、Clark Alex E.、Almanza Gonzalo、Zanetti Maurizio、Castro Andrea、Olmedillas Eduardo、Tsigelny Igor F.、Saphire Erica Ollmann
Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of SciencesDivision of Infectious Diseases and Global Public Health, Department of Medicine, University of California San DiegoLaboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, and School of Basic Medical Sciences, Capital Medical UniversitySan Diego Supercomputer Center, University of California at San DiegoDivision of Infectious Diseases and Global Public Health, Department of Medicine, University of California San DiegoThe Laboratory of Immunology, Department of Medicine and Moores Cancer Center, University of California San DiegoThe Laboratory of Immunology, Department of Medicine and Moores Cancer Center, University of California San DiegoBiomedical Informatics Program, University of California San DiegoCenter for Infectious Disease and Vaccine Research, La Jolla Institute for ImmunologySan Diego Supercomputer Center, University of California at San DiegoCenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology
医学研究方法预防医学基础医学
Gao George F.,Carlin Aaron F.,Wu Yan,Kouznetsova Valentina,Clark Alex E.,Almanza Gonzalo,Zanetti Maurizio,Castro Andrea,Olmedillas Eduardo,Tsigelny Igor F.,Saphire Erica Ollmann.Structure-selected RBM immunogens prime polyclonal memory responses that neutralize SARS-CoV-2 variants of concern[EB/OL].(2025-03-28)[2025-05-26].https://www.biorxiv.org/content/10.1101/2021.10.01.462840.点此复制
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